Shades of Gray

The New England Journal of Medicine recently published an article of an OHRP determination and apparent backtrack with a mea culpa.

The article is slim on details, however, it appears a research protocol was being followed involving hand-washing using different sanitizing techniques and placement location in the insertion of central venous catheters to determine whether a protective effect exists based on the technique and/or placement strategy used.

Yet the authors suggest this study could have, and should have, been expedited under Category 4 and Category 5.

Expedited review can occur only when specific criteria are met. Category 4 states:

Collection of data through noninvasive procedures (not involving general anesthesia or sedation) routinely employed in clinical practice, excluding procedures involving x-rays or microwaves. Where medical devices are employed, they must be cleared/approved for marketing. (Studies intended to evaluate the safety and effectiveness of the medical device are not generally eligible for expedited review, including studies of cleared medical devices for new indications.)

Examples: (a) physical sensors that are applied either to the surface of the body or at a distance and do not involve input of significant amounts of energy into the subject or an invasion of the subject=s privacy; (b) weighing or testing sensory acuity; (c) magnetic resonance imaging; (d) electrocardiography, electroencephalography, thermography, detection of naturally occurring radioactivity, electroretinography, ultrasound, diagnostic infrared imaging, doppler blood flow, and echocardiography; (e) moderate exercise, muscular strength testing, body composition assessment, and flexibility testing where appropriate given the age, weight, and health of the individual.

Meanwhile, Category 5 reads:

Research involving materials (data, documents, records, or specimens) that have been collected, or will be collected solely for nonresearch purposes (such as medical treatment or diagnosis). (NOTE: Some research in this category may be exempt from the HHS regulations for the protection of human subjects. 45 CFR 46.101(b)(4). This listing refers only to research that is not exempt.)

Yet the protocol in question involving the placement of a catheter, appears to disqualify this study from Category 4 as a catheter placement is inherently invasive. In addition, the protocol also appears to vary placement of the catheter for comparison purposes in the hopes of acquiring generalizable conclusions (e.g., it is safer/better minimize the placement of the catheter at the femoral site).

45 CFR 46.102 defines research as:

Research means a systematic investigation, including research development, testing and evaluation, designed to develop or contribute to generalizable knowledge. Activities which meet this definition constitute research for purposes of this policy, whether or not they are conducted or supported under a program which is considered research for other purposes. For example, some demonstration and service programs may include research activities.

My sense is a reasonable person would concur this is research.

Therefore, if this is research, invasive, and data in part is collected for research purposes, it seems clear such a study would not qualify for expedited review.

How can so many people, including the federal body regulating IRBs come to so may different conclusions? One, someone at OHRP does not know what he is doing. Two, Johns Hopkins IRB/staff do not know what they're doing. Three, I don't know what I'm doing. Or four, in a world of "black and white" regulations, we live in an IRB world of frustrating grays.